Transcription in eukaryotes is a tightly regulated, multistep process. Gene-specific transcriptional activators, several different co-activators and general transcription factors are necessary to ...access specific loci to allow precise initiation of RNA polymerase II transcription. As the dense chromatin folding of the genome does not allow the access of these sites by the huge multiprotein transcription machinery, remodelling is required to loosen up the chromatin structure for successful transcription initiation. In the present review, we summarize the recent evolution of our understanding of the function of two histone acetyl transferases (ATs) from metazoan organisms: GCN5 and PCAF. Their overall structure and the multiprotein complexes in which they are carrying out their activities are discussed. Metazoan GCN5 and PCAF are subunits of at least two types of multiprotein complexes, one having a molecular weight of 2 MDa (SPT3-TAF9-GCN5 acetyl transferase/TATA binding protein (TBP)-free-TAF complex/PCAF complexes) and a second type with about a size of 700 kDa (ATAC complex). These complexes possess global histone acetylation activity and locus-specific co-activator functions together with AT activity on non-histone substrates. Thus, their biological functions cover a wide range of tasks and render them indispensable for the normal function of cells. That deregulation of the global and/or specific AT activities of these complexes leads to the cancerous transformation of the cells highlights their importance in cellular processes. The possible effects of GCN5 and PCAF in tumorigenesis are also discussed.
Highlights • The pathophysiology of stroke is interpreted in the concept of neurovascular unit. • System biology approach provides a new insight into ischemic-reperfusion injury. • The only effective ...therapy in stroke is early reperfusion with its inherent limitations. • Acceleration of post-ischemic vascular remodeling and neuronal plasticity is still in preliminary phase.
The study aimed at a quantitative evaluation of macular vasculature after primary repair of rhegmatogenous retinal detachment (RRD) in correlation with the elapsed postoperative time. Optical ...coherence tomography angiography (OCT-A) was performed in 66 eyes of 33 patients in a retrospective case-control study: superficial and deep retinal vessel density (VD) of the whole image, fovea, parafovea, non-flow area, and foveal avascular zone (FAZ) were measured. Data of eyes with RRD were compared to the healthy fellow eyes in 3 groups according to the elapsed time after surgery: RD1: 6–12 months (n = 10), RD2: 1–2 years (n = 10), and RD3: 2–10 years (n = 13). In RD1 VD was significantly lower in the superficial parafoveal, deep parafoveal, and deep whole area compared to the fellow eyes. In RD3 VD was significantly lower in the superficial fovea, parafovea, whole image, and deep fovea, the non-flow area was significantly enlarged. OCT-A demonstrated a significant reduction in the superficial and deep regions of the macular vasculature after the repair of RRD. The deep area is more affected in the early postoperative period and the superficial region and the extent of the non-flow area are more involved after a longer postoperative time.
A novel methodology is presented for the systematic design of setpoint operating curves and seed recipes for supersaturation controlled crystallization processes. A design parameter for ...supersaturation controlled processes is introduced as a function of supersaturation, time and growth kinetics. Based on this parameter and a simplified analytical model, the supersaturation and batch time can be determined for any supersaturation controller crystallisation process, using an optimization approach to obtain a target distribution with desired shape. The approach also gives the temperature profile versus time corresponding to a particular constant supersaturation, providing a direct design approach for practical applications. Additionally, two methods are proposed that use the seed in conjunction with the supersaturation design for CSD control. One designs the seed recipe as a mixture of crystals resulting from sieve analysis, whereas the second evaluates a dynamic seed addition profile, which is able to achieve complex target CSDs. The proposed methods are exemplified for the model system of potash alum in water.
▸ An analytical CSD estimator is derived for crystallisation at constant supersaturation. ▸ A supersaturation controlled crystallisation design parameter is introduced. ▸ Design parameter is determined via optimisation for target CSD shape. ▸ Combined supersaturation and seed recipe optimisation is proposed for CSD shaping. ▸ Analytical estimator is used to evaluate and design dynamic seeding procedures.
Context.
The spatial distribution of molecules around starless cores is a powerful tool for studying the physics and chemistry governing the earliest stages of star formation.
Aims.
Our aim is to ...study the chemical differentiation in starless cores to determine the influence of large-scale effects on the spatial distribution of molecules within the cores. Furthermore, we want to put observational constraints on the mechanisms responsible in starless cores for the desorption of methanol from the surface of dust grains where it is efficiently produced.
Methods.
We mapped methanol, CH
3
OH, and cyclopropenylidene,
c
-C
3
H
2
, with the IRAM 30 m telescope in the 3 mm band towards six starless cores embedded in different environments, and in different evolutionary stages. Furthermore, we searched for correlations among physical properties of the cores and the methanol distribution.
Results.
From our maps we can infer that the chemical segregation between CH
3
OH and
c
-C
3
H
2
is driven by uneven illumination from the interstellar radiation field (ISRF). The side of the core that is more illuminated has more C atoms in the gas-phase and the formation of carbon-chain molecules like
c
-C
3
H
2
is enhanced. Instead, on the side that is less exposed to the ISRF the C atoms are mostly locked in carbon monoxide, CO, the precursor of methanol.
Conclusions.
We conclude that large-scale effects have a direct impact on the chemical segregation that we can observe at core scale. However, the non-thermal mechanisms responsible for the desorption of methanol in starless cores do not show any dependency on the H
2
column density at the methanol peak.
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•Coupled analysis of PV generation and building energy using adaptive BIPV shading.•20–80% net energy saving compared to an equivalent static system.•The system can in some cases ...compensate for the entire heating/cooling/lighting load.•High resolution radiation simulation including impacts of module self shading.
The utilisation of a dynamic photovoltaic system for adaptive shading can improve building energy performance by controlling solar heat gains and natural lighting, while simultaneously generating electricity on site. This paper firstly presents an integrated simulation framework to couple photovoltaic electricity generation to building energy savings through adaptive shading. A high-resolution radiance and photovoltaic model calculates the photovoltaic electricity yield while taking into account partial shading between modules. The remaining solar irradiation that penetrates the window is used in a resistance-capacitance building thermal model. A simulation of all possible dynamic configurations is conducted for each hourly time step, of which the most energy efficient configuration is chosen. We then utilise this framework to determine the optimal orientation of the photovoltaic panels to maximise the electricity generation while minimising the building’s heating, lighting and cooling demand. An existing adaptive photovoltaic facade was used as a case study for evaluation. Our results report a 20–80% net energy saving compared to an equivalent static photovoltaic shading system depending on the efficiency of the heating and cooling system. In some cases the Adaptive Solar Facade can almost compensate for the entire energy demand of the office space behind it. The control of photovoltaic production on the facade, simultaneously with the building energy demand, opens up new methods of building management as the facade can control both the production and consumption of electricity.
Controlling polymorphism is one of the most difficult challenges for the pharmaceutical industry. Polymorphs of the same compound can have very different properties that might affect the quality of ...the final drug. Many studies have focused on trying to determine robust methods to produce specific polymorphs that exhibit the desired characteristics of the drug (solubility and rate of dissolution in particular). The choice of solvent, pH, kinetic conditions and the presence of impurities can all have very strong effects on the polymorphic outcome of cooling crystallization. In this work, the crystallization of
ortho
-aminobenzoic acid (OABA) in the presence of a structurally related additive (benzoic acid) will be studied using both
in situ
PAT tools and offline techniques. The effect on morphology, polymorphic outcome, polymorphic transformation kinetics and tendency towards agglomeration in different solvents will be studied using a large variety of instrumentation. The incorporation of benzoic acid in solid solution in the three different polymorphs of OABA will also be quantified and discussed. The results of the crystallization experiments and offline analysis will be compared and interpreted using the information on the crystal structures of the three OABA polymorphs from the Cambridge Crystallographic database.
The crystal shape and polymorphism of
ortho
-aminobenzoic acid were tailored using combinations of solvents and a structurally related additive.
Context. L1521E is a dense starless core in Taurus that was found to have relatively low molecular depletion by earlier studies, thus suggesting a recent formation. Aims. We aim to characterize the ...chemical structure of L1521E and compare it to the more evolved L1544 pre-stellar core. Methods. We have obtained ~2.5 × 2.5 arcminute maps toward L1521E using the IRAM-30 m telescope in transitions of various species, including C17O, CH3OH, c-C3H2, CN, SO, H2CS, and CH3CCH. We derived abundances for the observed species and compared them to those obtained toward L1544. We estimated CO depletion factors using the C17O IRAM-30 m map, an N(H2) map derived from Herschel/SPIRE data and a 1.2 mm dust continuum emission map obtained with the IRAM-30 m telescope. Results. Similarly to L1544, c-C3H2 and CH3OH peak at different positions. Most species peak toward the c-C3H2 peak including C2S, C3S, HCS+, HC3N, H2CS, CH3CCH, and C34S. C17O and SO peak close to both the c-C3H2 and the CH3OH peaks. CN and N2H+ peak close to the Herschel dust peak. We found evidence of CO depletion toward L1521E. The lower limit of the CO depletion factor derived toward the Herschel dust peak is 4.3±1.6, which is about a factor of three lower than toward L1544. We derived abundances for several species toward the dust peaks of L1521E and L1544. The abundances of most sulfur-bearing molecules such as C2S, HCS+, C34S, C33S, and HCS+ are higher toward L1521E than toward L1544 by factors of ~2–20, compared to the abundance of A-CH3OH. The abundance of methanol is very similar toward the two cores. Conclusions. The fact that the abundances of sulfur-bearing species toward L1521E are higher than toward L1544 suggests that significant sulfur depletion takes place during the dynamical evolution of dense cores, from the starless to pre-stellar stage. The CO depletion factor measured toward L1521E suggests that CO is more depleted than previously found. Similar CH3OH abundances between L1521E and L1544 hint that methanol is forming at specific physical conditions in the Taurus Molecular Cloud Complex, characterized by densities of a few ×104 cm−3 and N(H2) ≳ 1022 cm−2, when CO starts to catastrophically freeze-out, while water can still be significantly photodissociated, so that the surfaces of dust grains become rich in solid CO and CH3OH, as already found toward L1544. Methanol can thus provide selective crucial information about the transition region between dense cores and the surrounding parent cloud.
In patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, the addition of daratumumab to bortezomib, melphalan, and prednisone increased progression-free ...survival and the response rate at the cost of an increase in infections.
To measure and compare sizing and positioning parameters of femtosecond laser capsulotomy with manual continuous curvilinear capsulorrhexis (CCC).
Femtosecond capsulotomies (Alcon-LenSx Lasers Inc) ...and CCC were carried out in 20 eyes of 20 patients, respectively. Intraocular lens (IOL) decentration, circularity, vertical and horizontal diameters of capsulotomies, and capsule overlap were measured with Adobe Photoshop (Adobe Systems Inc) 1 week, 1 month, and 1 year after surgery. Between-group differences of parameters and predictors of IOL decentration were determined with repeated measures analysis of variance, chi-square test, and logistic regression analyses.
Vertical diameter of CCC was statistically significantly higher in the first week and month. Significantly higher values of capsule overlap over 1 year and circularity in the first week showed more regular femtosecond capsulotomies. Horizontal IOL decentration was statistically significantly higher in the CCC group over 1 year. A significant difference was noted between the two groups in dichotomized horizontal decentration values at 0.4 mm with chi-square test after 1 week and 1 year (P=.035 and P=.016, respectively). In univariable general estimating equation models, type of capsulorrhexis (P<.01) and capsule overlap (P=.002) were significant predictors of horizontal decentration. Vertical diameter showed significant correlation to the overlap in the CCC group (1 week: r=-0.91; 1 month: r=-0.76, P<.01; 1 year: r=-0.62, P<.01), whereas no significant correlation was noted in the femtosecond group (P>.05).
More precise capsulotomy sizing and centering can be achieved with femtosecond laser. Properly sized, shaped, and centered femtosecond laser capsulotomies resulted in better overlap parameters that help maintain proper positioning of the IOL.
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